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Christian Kjer Heerfordt,1 Josefin Eklöf,1 Pradeesh Sivapalan,1 Truls Sylvan Ingebrigtsen,1 Tor Biering-Sørensen,2– 4 Zitta Barrella Harboe,4,5 Jesper Koefod Petersen,6,7 Christian Østergaard Andersen,8 Jonas Bredtoft Boel,9 Anne Kathrine Bock,10 Alexander G Mathioudakis,11,12 John R Hurst,13 Shailesh Kolekar,7 Sofie Lock Johansson,14 Jette Marie Bangsborg,9 Jens Otto Jarløv,9 Ram Benny Dessau,15 Christian Borbjerg Laursen,14,16 Michael Perch,4,17 Jens-Ulrik Stæhr Jensen1,4,18 1Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark; 2Department of Cardiology, Herlev and Gentofte Hospital, Cardiovascular Non-Invasive Imaging Research Laboratory, University of Copenhagen, Copenhagen, Denmark; 3Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark; 4Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 5Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark; 6Department of Respiratory Medicine, Zealand University Hospital Naestved, Naestved, Denmark; 7Department of Pulmonary Medicine, Zealand University Hospital, Roskilde, Denmark; 8Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark; 9Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark; 10Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 11The North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 12Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 13UCL Respiratory, University College London, London, UK; 14Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark; 15Department of Clinical Microbiology, Zealand University Hospital, Slagelse Hospital, Slagelse, Denmark; 16Institute for Clinical Research, University of Southern Denmark, Odense, Denmark; 17Department of Cardiology, Section for Lung Transplantation, Rigshospitalet, Copenhagen, Denmark; 18PERSIMUNE & CHIP: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Christian Kjer Heerfordt, Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark, Tel +4523303431, Email christian.kjer.heerfordt@regionh.dkBackground: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users.Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010– 2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses.Findings: A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with S. pneumoniae during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results.Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring S. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.Keywords: COPD, inhaled corticosteroids, Streptococcus pneumoniae, clinical epidemiology

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

We examined the added value of perineal swabs in addition to nose and throat swabs when screening for Methicillin-resistant Staphylococcus aureus colonization, and risk factors for perineal carriage in 6,642 patients. In our mainly primary care setting, the added value was 9.3%. Patients <3 or ≥80 had the highest risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests that could have influenced the work reported in this paper. All authors have seen and approved the final version of the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients with immediate type allergic reactions to penicillins are at risk of anaphylaxis on reexposure. Diagnostic gold standard is drug provocation test (DPT) if allergy is not diagnosed by other means, such as skin testing or in vitro testing with measurement of specific IgE. Specific IgE testing carries low risk for the patient and blood sampling can be performed in primary care, but it is reported to have low sensitivity. The aim of this study was to evaluate if clinical characteristics of patients with suspected allergic reactions to penicillin and elevated specific IgE to penicillins, differed from patients without specific IgE, to identify predictors for elevated specific IgE to penicillins., Methods: Levels of specific IgE to five penicillins (penicillin G, penicillin V, amoxicillin, ampicillin, and penicillin minor determinants) were available for 9,100 patients. Using multiple logistic regression, clinical data from 430 patients in this group who had elevated specific IgE to one or more penicillins were compared to data from 4,094 patients without specific IgE to penicillins, who had undergone DPT with a penicillin., Results: In total 5.2% of patients had elevated specific IgE to one or more penicillins. Significantly more patients with elevated specific IgE had a history of immediate type reactions (&lt;2 h) (OR = 4.34, p &lt; 0.001); circulatory symptoms (OR = 1.63, p = 0.03) or angioedema (OR = 1.46, p = 0.005). Also, significantly more patients with elevated specific IgE had been treated with adrenaline (OR = 2.21, p = 0.005), steroids (OR = 1.76, p &lt; 0.001), or antihistamines (OR = 1.83, p &lt; 0.001)., Conclusion: A history of an immediate type reaction requiring treatment, combined with elevated specific IgE to one or more penicillins is suggestive of an IgE mediated penicillin allergy and further allergy investigations may not be needed. Specific IgE to penicillins may be used early in allergy investigation of patients with severe immediate type reactions to penicillins., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Efforts to delabel penicillin allergic patients are important as the majority of suspected penicillin allergy can be ruled out by relevant allergy testing. The aim is to change the antibiotic pattern in delabeled patients to minimize use of unnecessary broad-spectrum antibiotics, reducing the risk of antimicrobial resistance and making treatment more cost effective. However, published information on subsequent antibiotic use is scarce. To evaluate the effect of delabeling on subsequent antibiotic use in primary care, a cohort of 2911 patients tested for penicillin allergy was compared to a matched control group of 14,522 individuals from the background population. In total 86.4% of the tested patients were delabeled. For delabeled patients, penicillin use increased from 0.07 prescriptions per patient year before allergy investigation, to 0.53 prescriptions per patient year post investigation (p < 0.001). The use of fluoroquinolones and macrolides was reduced and reached a level comparable to the background population. This study shows that penicillin allergy delabeling has significant positive impact on subsequent antibiotic use in primary care, and that penicillin use increases to levels similar to the background population. Penicillin allergy delabeling should be prioritized as an important and efficient element in antimicrobial stewardship initiatives., Competing Interests: The authors report no competing interests., (© 2024 The Authors.)

Objectives: Bacteremia is an acute severe infection with high mortality. Changes in healthcare services and coinfections with SARS-CoV-2 may have affected the mortality for bacteremia during the COVID-19 pandemic, which has been reported for other major diseases. In this study we examine the all-cause bacteremia mortality amidst the COVID-19 pandemic., Methods: A population-based cohort study comprised of laboratory confirmed bacteremia episodes in the Capital Region, Denmark (March 2019-February 2022). Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI) for all-cause bacteremia mortality associated with the Covid-19 restriction period, a strike period, and coinfection with SARS-CoV-2, adjusted for possible confounders., Results: A total of 14,912 bacteremia episodes were identified in 12,693 patients during the study period. The 30- and 90-day all-cause mortality were 19 % and 27 %, respectively. The fully adjusted HR for 30- and 90-day all-cause mortality associated with the Covid-19 restriction period were 0.91 (95 % CI, 0.84 to 0.99) and 0.90 (95 % CI, 0.84 to 0.96), respectively, compared to the remaining time period. The corresponding HRs associated with SARS-CoV-2 coinfection were 1.29 (95 % CI, 1.11 to 1.50) and 1.36 (95 % CI, 1.20 to 1.55) compared to patients without coinfection. The association between the national nurse strike and all-cause bacteremia mortality was inconclusive., Conclusions: In this large population-based cohort study, a significant reduction in all-cause mortality for bacteremia was observed during the Covid-19 restriction period in Denmark, while coinfection with SARS-CoV-2 seem to be a substantial risk factor for all-cause bacteremia mortality., Competing Interests: All authors affirm that this manuscript is conducted honest, accurate, and transparent. All authors have completed the author submission statement. All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (© 2024 The Authors.)

Background: Decolonization treatment of MRSA carriers is recommended in Denmark, except in households with MRSA-positive children <2 years old (wait-and-see approach)., Objectives: To investigate a wait-and-see approach in children 2-5 years old, and the effect of decolonization treatment of MRSA carriage in all children <6 years old., Patients and Methods: In this retrospective follow-up study, we included MRSA carriers <6 years old in the Capital Region of Denmark from 2007 to 2021. Data were collected from laboratory information systems and electronic patient records. We divided children into age groups of <2 years or 2-5 years and decolonization treatment versus no treatment. Treatment was chlorhexidine body washes and nasal mupirocin, sometimes supplemented with systemic antibiotics. Children were followed until becoming MRSA free, or censoring. The probability of becoming MRSA free was investigated with Cox regression (higher HRs indicate faster decolonization)., Results: Of 348 included children, 226 were <2 years old [56/226 (25%) received treatment] and 122 were 2-5 years old [90/122 (74%) received treatment]. Multivariable analyses did not show a larger effect of decolonization treatment versus no treatment in <2-year-olds (HR 0.92, 95% CI 0.52-1.65) or 2-5-year-olds (HR 0.54, 95% CI 0.26-1.12). Without treatment, 2-5-year-olds tended to clear MRSA faster than <2-year-olds (HR 1.81, 95% CI 0.98-3.37)., Conclusions: We did not find a larger effect of decolonization treatment versus no treatment in children <6 years old, and 2-5-year-olds tended to become MRSA free faster than <2-year-olds. These results support a wait-and-see approach for all children <6 years old, but further studies are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: Inhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.We aimed to determine whether an association between a lower respiratory tract culture with Stenotrophomonas maltophilia and increasing ICS dosing in patients with COPD exists., Design: An observational cohort study of outpatients with COPD in Denmark between 2010 and 2018.ICS exposure was categorised into four groups based on average daily consumption 1 year prior to inclusion: no use, low ICS dose (≤400 µg), moderate ICS dose (400-800 µg) and high ICS dose (>800 µg). Dose-response relationship was investigated by a multivariable Cox proportional hazards regression., Results: Of the total 22 689 patients, 459 had lower respiratory tract cultures positive for S. maltophilia . The HR of S. maltophilia increased with increasing daily ICS dose: low ICS dose HR 2.6 (95% CI 1.6 to 4.0), moderate ICS dose HR 3.0 (95% CI 1.9 to 4.6) and high ICS dose HR 5.7 (95% CI 3.8 to 8.5)., Conclusions: We found that ICS was associated with a high, dose-dependent increased hazard of S. maltophilia in outpatients with COPD. High dose users had a nearly six times increased hazard compared with non-users of ICS. When appropriate, attempts at de-escalating ICS treatment should be made., Competing Interests: Competing interests: Outside the submitted work, RBD has been on an advisory board for Pfizer. CSU has received grants from Sanofi, Boehringer Ingelheim, AstraZeneca and Novartis; consulting fees from Chiesi, Orion Pharma, AstraZeneca, GSK and TEVA; speaker fees from Orion Pharma, AstraZeneca and TEVA; and been on advisory boards for Novartis, Sanofi, Glaxo-Smith Kline, Chiesi, AstraZeneca and Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD., Methods: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression., Results: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1)., Conclusions: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. Moraxella catarrhalis is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with M. catarrhalis in patients with COPD., Objective: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with M. catarrhalis ., Methods: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for M. catarrhalis . For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained., Results: We found an increased, dose-dependent, risk of a lower respiratory tract sample with M. catarrhalis among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95% CI 1.19 to 2.30, p=0.003) and 1.82 (95% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of M. catarrhalis was 2.80 (95% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population., Conclusion: Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure., Competing Interests: Competing interests: RBD reports having received payment for expert testimony. Remaining authors have no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Penicillin allergy labels have been shown to be associated with suboptimal treatment, negative health outcomes, and increased antibiotic resistance. Many inpatients claim to have penicillin allergy, but studies show that allergy can be disproved and the label removed in up to 90% of cases., Objectives: The purpose of the study was to investigate the proportion of patients with a penicillin allergy label in a Danish hospital and to classify patients according to the risk of having penicillin allergy in "no risk," low, and high risk., Methods: For 22 days, inpatients with penicillin allergy labels were interviewed, had their dispensed penicillin prescriptions examined, and were subsequently categorized into risk groups based on the risk evaluation criteria in national guidelines., Results: In total, 260 patients had a penicillin allergy label (10% of the inpatients). Out of 151 included patients, 25 were "no risk" patients (17%), who could potentially have their penicillin allergy label removed without testing. 42 were low-risk patients (28%). 10 "no risk" patients and 20 low-risk patients had been prescribed and dispensed one or more penicillins despite an allergy label., Conclusion: Ten percent of inpatients have a penicillin allergy label in a Danish hospital. 17% of these could potentially have their penicillin allergy label removed without allergy testing., (© 2023 S. Karger AG, Basel.)

Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a positive Haemophilus influenzae airway culture with use of ICS in outpatients with COPD. Study Design and Methods: We conducted an epidemiological cohort study using data from 1 January 2010 to 19 February 2018, including 21,218 outpatients with COPD in Denmark. ICS use 365 days prior to cohort entry was categorised into low, moderate, and high, based on cumulated ICS dose extracted from a national registry on reimbursed prescriptions. A Cox proportional hazards regression model was used to assess the future risk of acquiring H. Influenzae within 365 days from cohort entry, and sensitivity analyses were performed using propensity score matched models. Results: In total, 801 (3.8%) patients acquired H. Influenzae during follow-up. Use of ICS was associated with a dose-dependent increased risk of acquiring H. Influenzae with hazard ratio (HR) 1.2 (95% confidence interval (CI) 0.9−1.5, p value = 0.1) for low-dose ICS; HR 1.7 (95% CI 1.3−2.1, p value < 0.0001) for moderate dose; and HR 1.9 (95% CI 1.5−2.4, p value < 0.0001) for high-dose ICS compared to no ICS use. Results were confirmed in the propensity-matched model using the same categories. Conclusions: ICS use in outpatients with COPD was associated with a dose-dependent increase in risk of isolating H. Influenzae. This observation supports that high dose ICS should be used with caution.

Background: Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD., Methods: We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa . Propensity score matched models were used as sensitivity analyses., Results: A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001)., Conclusion: Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa . Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings., Competing Interests: Competing interests: RBD reports grants and personal fees from Roche, outside the submitted work. TSI reports personal fees from AstraZeneca, outside the submitted work. PS reports non-financial support from Novartis and personal fees from Boehringer Ingelheim, outside the submitted work. HM is a member of ALK-Abelló Nordic A/S advisory board., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Penicillin allergy is suspected in 10% of hospital inpatients but can be disproved in 90% of cases. Direct oral provocation without preceding tests among low-risk patients has proven to be safe in studies of both children and adults and is gaining use across the world. The aims of this study were to investigate the rate of severe allergic reactions to direct oral drug provocation, without preceding tests, in penicillin allergy patients stratified to be at low risk, as well as to examine if these patients have barriers to penicillin allergy de-labeling and future use of penicillins., Methods: Adult patients referred to a university hospital allergy clinic with a suspected penicillin allergy were prospectively risk evaluated. Patients stratified to be at low risk were offered a direct oral provocation with a single-dose amoxicillin followed by 4 days of continued treatment. The same risk stratification criteria were applied to a larger retrospective cohort., Results: In the prospective study population, 202 patients had a direct oral drug provocation and 20 (10%) were positive. There were no cases of anaphylaxis or severe delayed hypersensitivity. Fifteen reactions were benign rashes with onset >1 day after initial dosing, and 13 of these were maculopapular rashes. The same low-risk criteria were applied retrospectively to patients in a drug provocation database, and 1,759 patients fulfilled the criteria; of these, 10% had positive provocations, and there were no cases of anaphylaxis or severe delayed hypersensitivity. De-labeled patients in the prospective study reported not to fear future penicillin intake, after prolonged provocation., Conclusion: The risk stratification criteria for identifying low-risk patients for the oral drug provocation test without prior skin testing were safe in terms of avoiding anaphylaxis or severe delayed hypersensitivity. Benign delayed skin reactions still occurred, and access to allergy advice and follow-up is necessary., (© 2022 S. Karger AG, Basel.)

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)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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 < 0.01) and 2.48 (95% CI 1.04-5.93, P = 0.04), respectively, compared with mecillinam., 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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

Objectives: The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD., Methods: This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination., Results: A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartile-range: 427-1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2-3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3-3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients 'ever colonized' with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization., Conclusions: COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142)., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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

A high incidence of Clostridium difficile and multiresistant organisms and increasing consumption of cephalosporins and quinolones have required an antibiotic stewardship programme, and antibiotic audits with feedback, revised guidelines and stringent prescription rules have been successful. The hospital intervention was managed by an antibiotic team combined with contact persons in all departments, a pocket edition of the guideline was available, and monthly commented reports about antibiotic consumption in each department were presented on the intranet. Significant declining use of restricted antibiotics was observed.