Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication in Patients With Brain Abscess in Denmark.

BACKGROUND: It is unknown whether patients diagnosed with brain abscess have an increased risk of psychiatric disorders. METHODS: In this nationwide, population-based matched cohort study from Denmark, we compared the incidence of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medications between patients diagnosed with brain abscess and individuals from the general population, matched on date of birth, sex, and residential area. RESULTS: We included 435 patients diagnosed with brain abscess and 3909 individuals in the comparison cohort: 61% were male and median age was 54 years. Patients diagnosed with brain abscess were more likely to suffer from comorbidity. The risk of a hospital diagnosis of psychiatric disorders was increased the first 5 years of observation. In the subpopulation, who had never been in contact with psychiatric hospitals or received psychiatric medication before study inclusion, the risk of developing psychiatric disorders was close to that of the background population, especially when we excluded dementia from this outcome. There was a substantial increase in the receipt of anxiolytics and antidepressants. The difference in the proportion of individuals who received anxiolytics and antidepressants increased from 4% (95% confidence interval [CI], 0%-7%) and 2% (95% CI, -1% to 5%) 2 years before study inclusion to 17% (95% CI, 12%-21%) and 11% (95% CI, 7%-16%) in the year after study inclusion. CONCLUSIONS: Patients with brain abscess without prior psychiatric disorders or receipt of psychiatric medicine are not at increased risk psychiatric disorders diagnosed in psychiatric hospitals, but they have an increased receipt of psychiatric medication.

Delabeling of Penicillin Allergy: Room for Improvement.

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.

The association between Staphylococcus aureus colonization on cheek skin at 2†months and subsequent atopic dermatitis in a prospective birth cohort.

BACKGROUND: Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. OBJECTIVES: To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. METHODS: In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. RESULTS: At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. CONCLUSIONS: It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.

Intravenous mecillinam compared with other ß-lactams as targeted treatment for Escherichia coli or Klebsiella spp. bacteraemia with urinary tract focus.

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 ß-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.

Antibiotic treatment in acute exacerbation of COPD: patient outcomes with amoxicillin vs. amoxicillin/clavulanic acid-data from 43,636 outpatients.

BACKGROUND: For antibiotic treatment of Acute exacerbations of COPD (AECOPD) the National guidelines in Denmark recommend either first choice amoxicillin 750 mg TID (AMX) or amoxicillin with clavulanic acid 500 mg/125 mg TID (AMC). Addition of clavulanic acid offers a broader spectrum; opposite, AMX alone in a higher dose may offer more time above MIC. The aim of this study was to determine which of these regimens is associated with better outcome. METHODS: The Danish Registry of COPD (DrCOPD), a nationwide outpatient COPD registry, was crosslinked with medication data and hospital contacts. The first prescription of AMX or AMC after inclusion in DrCOPD was used as exposure variable. Adjusted Cox proportional hazards models were used to analyze the risk of hospitalization or death (combined) within 30 days and other endpoints. RESULTS: For the first treatment of AECOPD 12,915 received AMX, and 30,721 patients received AMC. AMX was associated with a decreased risk of pneumonia hospitalization or death (aHR 0.6, 95% CI 0.5-0.7; p < 0.0001) compared to AMC. CONCLUSION: In AECOPD, empirically adding clavulanic acid to amoxicillin is not associated with a better outcome; it seems safe for these patients to be treated with amoxicillin alone.

Community-acquired meningitis caused by beta-haemolytic streptococci in adults: a nationwide population-based cohort study.

The objective of this study was to examine the clinical presentation of community-acquired beta-haemolytic streptococcal (BHS) meningitis in adults. This is a nationwide population-based cohort study of adults (≥ 16 years) with BHS meningitis verified by culture or polymerase chain reaction of the cerebrospinal fluid (CSF) from 1993 to 2005. We retrospectively evaluated clinical and laboratory features and assessed outcome by Glasgow Outcome Scale (GOS). We identified 54 adults (58% female) with a median age of 65 years (IQR 55-73). Mean incidence rate was 0.7 cases per 1,000,000 person-years. Alcohol abuse was noted among 11 (20%) patients. Group A streptococci (GAS) were found in 17 (32%) patients, group B (GBS) in 18 (34%), group C (GCS) in four (8%) and group G (GGS) in 14 (26%). Patients with GAS meningitis often had concomitant otitis media (47%) and mastoiditis (30%). Among patients with GBS, GCS or GGS meningitis, the most frequent concomitant focal infections were bone and soft tissue infections (19%) and endocarditis (16%). In-hospital mortality was 31% (95% CI 19-45), and 63% (95% CI 49-76) had an unfavourable outcome at discharge (GOS < 5). BHS meningitis in adults is primarily observed among the elderly and has a poor prognosis. GAS meningitis is primarily associated with concomitant ear-nose-throat infection.

The effect of short-course gentamicin therapy on kidney function in patients with bacteraemia-a retrospective cohort study.

The nephrotoxic potential of aminoglycosides is primarily correlated to the duration of therapy. However, there are discrepancies between previous studies regarding the effect of short course treatment. The aim of this study was to compare renal function, renal recovery and mortality in a large cohort of patients with bacteraemia, who were empirically treated with regimens with and without a short course (≤ 3 days) of once daily dosing of gentamicin. This was a retrospective propensity score-matched cohort study based on all patients with bacteraemia in a Danish hospital in the period 2010-2013. We included 702 patients who received gentamicin, and 702 who did not receive gentamicin. To determine the impact of gentamicin on renal function, we used a modified version of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for acute kidney injury (AKI), and the resulting data were analyzed by logistic regression. We used Cox regression analysis to compare the adjusted mortality rates between the two groups. According to the KDIGO criteria, we found no significant difference in the occurrence of AKI between the two groups (odds ratio (OR) 0.90 (95% CI 0.68-1.20)). We found that recovery of renal function was similar in the two groups, OR 1.00 (95% CI 0.63-1.60). The hazard ratio for 90-day all-cause mortality was 1.02 (95% CI 0.84-1.25). Short-course empirical gentamicin treatment of patients with bacteraemia was not associated with an increased incidence of AKI nor all-cause mortality in this study, and we observed similar reversibility of renal function.

Impact of antibiotic restriction on resistance levels of Escherichia coli: a controlled interrupted time series study of a hospital-wide antibiotic stewardship programme.

OBJECTIVES: We evaluated the effect of an antibiotic stewardship programme (ASP) on the use of antibiotics and resistance levels of Escherichia coli using a method that allowed direct comparison between an intervention hospital and a control hospital. METHODS: The study was conducted as a retrospective controlled interrupted time series (ITS) at two university teaching hospitals, intervention and control, with 736 and 552 beds, respectively. The study period was between January 2008 and September 2014. We used ITS analysis to determine significant changes in antibiotic use and resistance levels of E. coli. Results were directly compared with data from the control hospital utilizing a subtracted time series (STS). RESULTS: Direct comparison with the control hospital showed that the ASP was associated with a significant change in the level of use of cephalosporins [-151 DDDs/1000 bed-days (95% CI -177, -126)] and fluoroquinolones [-44.5 DDDs/1000 bed-days (95% CI -58.9, -30.1)]. Resistance of E. coli showed a significant change in slope for cefuroxime [-0.13 percentage points/month (95% CI -0.21, -0.057)] and ciprofloxacin [-0.15 percentage points/month (95% CI -0.26, -0.038)]. CONCLUSIONS: The ASP significantly reduced the use of cephalosporins and fluoroquinolones, with concomitant decreasing levels of E. coli resistance to cefuroxime and ciprofloxacin. The same development was not observed at the control hospital.

Parents' socioeconomic factors related to high antibiotic prescribing in primary health care among children aged 0-6 years in the Capital Region of Denmark.

OBJECTIVE: To investigate the distribution of antibiotic prescriptions in primary health care among children aged 0-6 years and its association with socioeconomic factors. DESIGN: A cross-sectional study describing antibiotic prescriptions and socioeconomic factors, using different population-based registers from Statistics Denmark. SETTING: Antibiotic prescriptions in 2012 from primary health care in the Capital Region of Denmark. SUBJECTS: The population of children aged 0-6 years (n = 139,398) in the Capital Region of Denmark. MAIN OUTCOME MEASURES: High use of antibiotics identified by number of antibiotic prescriptions (≥ 3 prescriptions per year) and defined daily doses (DDD). A multinomial logistic regression analysis estimating the association between high antibiotic use and parents' education, employment status, income, child's sex, and ethnic background. RESULTS: Ten percent of children accounted for 25% of the total use DDD. There was a clear tendency that the risk for high antibiotic use increased as parental educational level decreased. The risk for high use was the highest among children of mothers and fathers with basic schooling ≤10 years (OR 1.60, 95% CI 1.29-1.98, and OR 1.60, 95% CI 1.34-1.91, respectively). Low income and unemployment were not associated with high antibiotic use. CONCLUSION: Socioeconomic factors can only partially explain differences in antibiotic use. Further research is needed to clarify the unequal distribution of antibiotic prescribing and the association between high antibiotic use and low educational level. This would provide valuable information in the planning of strategies to promote rational use of antibiotics among children. KEY POINTS The Capital Region of Denmark has the highest rate of antibiotic prescribing in Denmark. Preschool children are among the age groups with the highest use. Ten percent of the children accounted for 25% of the total antibiotic use. Low parental educational level was associated with increased antibiotic use. Parents' income or employment status was not found to be associated with high antibiotic use.

Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus.

spa typing of methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been done by PCR amplification and Sanger sequencing of the spa repeat region. At Hvidovre Hospital, Denmark, whole-genome sequencing (WGS) of all MRSA isolates has been performed routinely since January 2013, and an in-house analysis pipeline determines the spa types. Due to national surveillance, all MRSA isolates are sent to Statens Serum Institut, where the spa type is determined by PCR and Sanger sequencing. The purpose of this study was to evaluate the reliability of the spa types obtained by 150-bp paired-end Illumina WGS. MRSA isolates from new MRSA patients in 2013 (n = 699) in the capital region of Denmark were included. We found a 97% agreement between spa types obtained by the two methods. All isolates achieved a spa type by both methods. Nineteen isolates differed in spa types by the two methods, in most cases due to the lack of 24-bp repeats in the whole-genome-sequenced isolates. These related but incorrect spa types should have no consequence in outbreak investigations, since all epidemiologically linked isolates, regardless of spa type, will be included in the single nucleotide polymorphism (SNP) analysis. This will reveal the close relatedness of the spa types. In conclusion, our data show that WGS is a reliable method to determine the spa type of MRSA.

Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy.

BACKGROUND: Fluoroquinolones are extensively used as prophylaxis for transrectal ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone resistance and selection of multiresistant organisms warrant new prophylactic strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic activity and the combination of these agents has a broad coverage of the majority of microorganisms causing infectious complications after TRUBP and may be a valuable future prophylactic regimen. PATIENTS AND METHODS: This was a retrospective cohort study of 2624 men that underwent TRUBP at a Danish university hospital. The patients were divided into three groups. Group 1 (n = 1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid before and for 2 days after TRUBP. RESULTS: One hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%) and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing Enterobacteriaceae was observed from the period when ciprofloxacin was used as prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and amoxicillin/clavulanic acid was used (5.9%). CONCLUSIONS: The combination of pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for TRUBP from a clinical, bacteriological and ecological point of view as compared with ciprofloxacin.

Differences in the distribution of pathogens and antimicrobial resistance in bloodstream infections in migrants compared with non-migrants in Denmark.

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

A pre-post intervention study: Knowledge among parents about child infections and antibiotic use facilitated by maternal and child health nurses.

AIMS: To investigate parent's knowledge and beliefs of common infections and antibiotics in children before and after an educational intervention provided by maternal and child health nurses. Second, to investigate sociodemographic differences in parent's knowledge before and following the intervention. DESIGN: A prospective pre-post intervention study. The intervention consisted of a booklet with information about childhood infections delivered by maternal and child health nurses. METHODS: The study population included 344 parents with a child born during 2017 and residing in three Danish municipalities. Knowledge about infections and antibiotics were collected quantitatively through an online questionnaire before and after the intervention (August 2017-November 2018) and analysed using linear mixed models. RESULTS: Parental knowledge increased after the intervention. Parents with lower education and born in Denmark compared to parents with higher education and born in other countries experienced a higher increase in knowledge from baseline to follow-up.

Invasive procedures and risk of brain abscess: a nationwide, population-based case-control study.

OBJECTIVES: It is unknown whether invasive procedures are associated with brain abscess. METHODS: Nationwide, population-based, matched case-control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0-6 months before study inclusion. RESULTS: We identified 435 patients and 3909 controls. The level of comorbidity was higher among patients with brain abscess than among controls. A total of 48 cases (11%) had one or more invasive procedures 0-6 months before study inclusion (adjusted odds ratios (aOR) of 3.6 (95% confidence interval (CI): 2.5-5.1), a population attributable fractions of 8% (95% CI: 7-9)). In primary care, ear, nose and throat (ENT) procedures were associated with brain abscess (aOR of 4.0 (95% CI: 2.0-8.0)), but gastrointestinal endoscopies were not (aOR of 1.0 (95% CI: 0.3-3.2)). No bronchoscopies were performed in primary care. In the hospital-based setting, ENT procedures, bronchoscopies and gastrointestinal endoscopies were associated with an increased risk of brain abscess (aOR of 14.5 (95% CI: 4.8-43.8), 20.3 (95% CI: 3.8-110.1) and 3.4 (95% CI: 2.0-5.6), respectively). CONCLUSIONS: The association between invasive procedures and brain abscess was more pronounced in the hospital-based setting than in primary care.

Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring Streptococcus pneumoniae Infection. A Multiregional Epidemiological Study.

Background: 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.

Nosocomial transmission of community-associated methicillin-resistant Staphylococcus aureus in Danish Hospitals.

OBJECTIVES: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the epidemiology of MRSA infections worldwide. In contrast to hospital-associated MRSA (HA-MRSA), CA-MRSA more frequently affects healthy individuals, both with and without recent healthcare exposure. Despite obvious epidemiological differences, it is unknown whether differences in nosocomial transmissibility exist. We have, therefore, quantified the transmissibility, expressed by the single admission reproduction number (R(A)), of CA-MRSA and HA-MRSA in hospital settings in Denmark. METHODS: MRSA index cases and secondary cases were investigated in four hospitals in the Copenhagen area. Index cases were defined as non-isolated, non-screened patients with MRSA, and secondary cases were defined as persons carrying MRSA isolates-identical to that of the corresponding index-as identified through contact screening. CA-MRSA and HA-MRSA were categorized upon genotyping [CA-MRSA: t008-ST8, PVL+; t019-ST30, PVL+; t127-ST1, PVL+; t044-ST80, PVL+; and their related spa types; and HA-MRSA: all other (where ST stands for sequence type and PVL stands for Panton-Valentine leucocidin)]. A mathematical model was applied to determine the genotype-specific transmission rate (i.e. R(A)) of CA-MRSA and HA-MRSA strains. RESULTS: During the 7 year study period there were 117 MRSA index cases with subsequent post-contact screening (of 1108 patients and healthcare workers), revealing 22 outbreaks with a total of 52 secondary patients. R(A) values were 0.07 (95% CI 0.00-0.28) and 0.65 (95% CI 0.48-0.84) for CA-MRSA and HA-MRSA, respectively. CONCLUSIONS: In four Danish hospitals the nosocomial transmission rate of CA-MRSA was 9.3 times lower than that of HA-MRSA.

Antibiotic prescribing among elderly living in long-term care facilities versus elderly living at home: a Danish registry-based study.

BACKGROUND: The objective of this study was to compare antibiotic prescription rates in Denmark among elderly living in long-term care facilities to elderly living at home, with regards to total antibiotic use and antibiotic use for urinary tract infection. METHODS: This is an observational registry-based study. The study population included all elderly Danish residents aged ≥75 years in 2016. Linear regression models were used to examine the difference in antibiotic prescription rates between elderly living in long-term care facilities and elderly living at home. Results were adjusted for age, sex and comorbidity, the latter assessed via the Charlson Comorbidity Index. RESULTS: The study population consisted of 416,627 elderly. Regression models showed that elderly living in long-term care facilities were prescribed 1.7 [CI 1.7-1.7] prescriptions/individual/year more than elderly living at home. For urinary tract infections the difference between elderly living in long-term care facilities and elderly living at home was 1.2 [CI 1.2-1.3] prescriptions/individual/year. CONCLUSIONS: Elderly living in long-term care facilities have a higher antibiotic prescribing rate than elderly living at home, despite controlling for age, sex and comorbidity. This indicates that long-term care facilities continuously should be a focus for antibiotic stewardship interventions.

Socioeconomic functioning in patients with brain abscess - a nationwide, population-based cohort study in Denmark.

OBJECTIVES: Long-term functional outcomes of brain abscess remains sparsely elucidated. METHODS: Nationwide, population-based cohort study of all Danish patients with a culture verified brain abscess and a comparison cohort from the general population individually matched on date of birth and sex. RESULTS: Among 435 patients and 1740 members of the comparison cohort, 61% were men and median age was 54 years. In the year of study inclusion, patients with brain abscess had more hospital admission days, more outpatient visits and more sick leave days, compared with the comparison cohort. With time, these differences subsided. Brain abscess was associated with permanent lower employment rates and a higher risk of disability pension (difference of proportion employed of -26% (95% CI: -36% to -17%) and of proportion on disability pension of 29% (95% CI: 20% to 38%) 5 years after study inclusion). Two years after study inclusion, 1.4% of patients with brain abscess lived in residential care homes (difference of 1.1% (-0.2% to 2.5%)). CONCLUSIONS: In this nationwide, population-based cohort study, brain abscess was associated with permanently decreased employment rates. Only a minority were dependent on residential care residency following a diagnosis of brain abscess suggesting that severe disability is probably rare.

Use of Inhaled Corticosteroids and Risk of Acquiring Haemophilus influenzae in Patients with Chronic Obstructive Pulmonary Disease.

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.

Temporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis: A Nationwide Study.

Background Monitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in-hospital and long-term mortality, according to microbiological cause in patients with IE from 2010 to 2017. Methods and Results Linking Danish nationwide registries, we identified all patients with first-time IE. In-hospital and long-term mortality rates were assessed according to microbiological cause and compared using multivariable adjusted logistic regression analysis and Cox proportional hazard analysis, respectively. A total of 4123 patients were included. Staphylococcus aureus was the most frequent cause (28.1%), followed by Streptococcus species (26.0%), Enterococcus species (15.5%), coagulase-negative staphylococci (6.2%), and "other microbiological causes" (5.3%). Blood culture-negative IE was registered in 18.9%. The proportion of blood culture-negative IE declined during the study period, whereas no significant changes were seen for any microbiological cause. Patients with Enterococcus species were older and more often had a prosthetic heart valve compared with other causes. For Streptococcus species IE, in-hospital and long-term mortality (median follow-up, 2.3 years) were 11.1% and 58.5%, respectively. Compared with Streptococcus species IE, the following causes were associated with a higher in-hospital mortality: S aureus IE (odds ratio [OR], 3.48 [95% CI, 2.74-4.42]), Enterococcus species IE (OR, 1.48 [95% CI, 1.11-1.97]), coagulase-negative staphylococci IE (OR, 1.79 [95% CI, 1.21-2.65]), "other microbiological cause" (OR, 1.47 [95% CI, 0.95-2.27]), and blood culture-negative IE (OR, 1.99 [95% CI, 1.52-2.61]); and the following causes were associated with higher mortality following discharge (median follow-up, 2.9 years): S aureus IE (hazard ratio [HR], 1.39 [95% CI, 1.19-1.62]), Enterococcus species IE (HR, 1.31 [95% CI, 1.11-1.54]), coagulase-negative staphylococci IE (HR, 1.07 [95% CI, 0.85-1.36]), "other microbiological cause" (HR, 1.45 [95% CI, 1.13-1.85]), and blood culture-negative IE (HR, 1.05 [95% CI, 0.89-1.25]). Conclusions This nationwide study showed that S aureus was the most frequent microbiological cause of IE, followed by Streptococcus species and Enterococcus species. Patients with S aureus IE had the highest in-hospital mortality.