Michael Dalager-Pedersen

Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study

Background— Infections may trigger acute cardiovascular events, but the risk after community-acquired bacteremia is unknown. We assessed the risk for acute myocardial infarction and ischemic stroke within 1 year of community-acquired bacteremia. Methods and Results— This population-based cohort study was conducted in Northern Denmark. We included 4389 hospitalized medical patients with positive blood cultures obtained on the day of admission. Patients hospitalized with bacteremia were matched with up to 10 general population controls and up to 5 acutely admitted nonbacteremic controls, matched on age, sex, and calendar time. All incident events of myocardial infarction and stroke during the following 365 days were ascertained from population-based healthcare databases. Multivariable regression analyses were used to assess relative risks with 95% confidence intervals (CIs) for myocardial infarction and stroke among bacteremia patients and their controls. The risk for myocardial infarction or stroke was greatly increased within 30 days of community-acquired bacteremia: 3.6% versus 0.2% among population controls (adjusted relative risk, 20.86; 95% CI, 15.38–28.29) and 1.7% among hospitalized controls (adjusted relative risk, 2.18; 95% CI, 1.80–2.65). The risks for myocardial infarction or stroke remained modestly increased from 31 to 180 days after bacteremia in comparison with population controls (adjusted hazard ratio, 1.64; 95% CI, 1.18–2.27), but not versus hospitalized controls (adjusted hazard ratio, 0.95; 95% CI, 0.69–1.32). No differences in cardiovascular risk were seen after >6 months. Increased 30-day risks were consistently found for a variety of etiologic agents and infectious foci. Conclusions— Community-acquired bacteremia is associated with increased short-term risk of myocardial infarction and stroke.

Stroke in community-acquired bacterial meningitis: a Danish population-based study.

OBJECTIVES Stroke is a serious complication in community-acquired bacterial meningitis (CABM), but the incidence, predispositions, and outcome need further clarification; this pertains in particular to the impact of pre-existing atherosclerosis risk factors. Therefore, we aimed to assess these features in a retrospective population-based cohort study. METHODS We included all patients over 16 years of age with CABM in North Denmark Region, 1998-2010. All data were retrieved from the patient records. A Glasgow Outcome Scale score of 1-4 was defined as an unfavourable outcome and 5 as favourable. RESULTS We identified 152 episodes of CABM. In 22 (14%) of the episodes, the patient had a stroke; 15 strokes were ischaemic, three were haemorrhagic, and four were a combination of both. Age and atherosclerosis risk factors were not significantly associated with stroke. However, stroke was associated with a higher in-hospital mortality (27% vs. 16%; age adjusted risk ratio (age aj. RR) 1.43, 95% confidence interval (CI) 0.67-3.04), unfavourable outcome (86% vs. 37%; age adj. RR 2.09, 95% CI 1.59-2.75), and long-term sequelae among survivors (88% vs. 40%, age adj. RR 2.01, 95% CI 1.53-2.65) compared with patients without stroke. CONCLUSIONS Stroke is a common complication among adult CABM patients and is associated with long-term sequelae and possibly also death. However, stroke seemed not to be related to atherosclerosis risk factors.

Dexamethasone treatment and prognostic factors in community-acquired bacterial meningitis: A Danish retrospective population-based cohort study

Abstract Introduction: The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial and treatment outcomes and predictors of a poor prognosis must be assessed regularly. We aimed to describe the outcome of patients with CABM treated with dexamethasone and to assess the performance of the Dutch Meningitis Risk Score (DMRS). Methods: We retrospectively evaluated all adults with CABM in North Denmark Region, 1998–2012. Outcomes included in-hospital mortality and Glasgow Outcome Scale (GOS) score. A GOS score of 5 was categorized as a favourable outcome and scores of 1–4 as unfavourable. We used logistic analysis to compute relative risks (RRs) with 95% confidence intervals (CIs) for an unfavourable outcome adjusted for age, sex, and comorbidity. Results: We identified a total of 172 cases of CABM. In-hospital mortality was unaffected by the implementation of dexamethasone in 2003 (19% vs 20%). Dexamethasone treatment was associated with a prompt diagnosis of meningitis and a statistically insignificant decrease in the risk of an unfavourable outcome (33% vs 53%; adjusted RR 0.64, 95% CI 0.41–1.01) and in-hospital mortality (15% vs 24%; adjusted RR 0.72, 95% CI 0.35–1.48). Of the risk factors included in the DMRS, we found age and tachycardia to be significantly associated with an unfavourable outcome in the multivariate analyses. Conclusions: Patients treated with dexamethasone were more likely to have a favourable outcome, although statistical significance was not reached. Several parameters included in the Dutch risk score were also negative predictors in our cohort, although the entire risk score could not be validated due to a lack of data.

Venous thromboembolism after community-acquired bacteraemia: a 20-year danish cohort study.

Background Infections may increase the risk for venous thromboembolism (VTE), but little is known about VTE risk associated with community-acquired bacteraemia (CAB). We examined the risk for VTE within one year of CAB in comparison to that in matched controls. Methods We conducted a population-based cohort study in North Denmark 1992–2011, using data from high-quality health-care databases. We included 4,213 adult CAB patients who had positive blood cultures drawn on the day of hospital admission, 20,084 matched hospitalised controls admitted for other acute medical illness, and 41,121 matched controls from the general population. We computed 0–90 and 91–365 day absolute risks for hospital-diagnosed VTE and used regression analyses with adjustment for confounding factors to compare the risk for VTE in bacteraemia patients and controls. Results Among CAB patients, 1.1% experienced VTE within 90 days of admission and 0.5% during 91–365 days after admission. The adjusted 90-day odds ratio (OR) for VTE was 1.9 (95% CI 1.4–2.7) compared with hospitalised controls, and 23.4 (95% CI 12.9–42.6) compared with population controls. During 91–365 days after CAB admission, the VTE risk remained moderately increased (adjusted hazard ratio vs. hospitalised controls, 1.4; 95% CI 0.8–2.5, and vs. population controls, 1.9; 95% CI 1.0–3.3). Compared to hospitalised controls, the 90-day VTE risk increase was greater for Gram-positive infection (adjusted OR 2.5; 95% CI 1.6–4.1) than for Gram-negative infection (adjusted OR, 1.2; 95% CI 0.7–2.1), partly due to a high risk after Staphylococcus aureus infection (3.6%). Conclusion The risk for VTE is substantially increased within 90 days after community-acquired bacteraemia when compared to hospitalised controls and population controls. However, the absolute risk of VTE following CAB is low.

The effect of community-acquired bacteraemia on return to workforce, risk of sick leave, permanent disability pension and death: a Danish population-based cohort study

Objectives Little is known about the prognosis of community-acquired bacteraemia (CAB) in workforce adults. We assessed return to workforce, risk for sick leave, disability pension and mortality within 1 year after CAB in workforce adults compared with blood culture-negative controls and population controls. Design Population-based cohort study. Setting North Denmark, 1996–2011. Participants We used population-based healthcare registries to identify all patients aged 20–58 years who had first-time blood cultures obtained within 48 h of medical hospital admission, and who were part of the workforce (450 bacteraemia exposed patients and 6936 culture-negative control patients). For each bacteraemia patient, we included up to 10 matched population controls. Primary and secondary outcome measures Return to workforce, risk of sick leave, permanent disability pension and mortality within 1 year after bacteraemia. Regression analyses were used to compute adjusted relative risks (RRs) with 95% CIs. Results One year after admission, 78% of patients with CAB, 85.7% of culture-negative controls and 96.8% of population controls were alive and in the workforce, and free from sick leave or disability pension. Compared with culture-negative controls, bacteraemia was associated with an increased risk for long-term sick leave (4-week duration, 40.2% vs 23.9%, adjusted RR, 1.51; CI 1.34 to 1.70) and an increased risk for mortality (30-day mortality, 4% vs 1.4%, adjusted RR, 2.34, CI 1.22 to 4.50; 1-year mortality, 8% vs 3.9%, adjusted RR, 1.73; CI 1.18 to 2.55). Bacteraemia patients had a risk for disability pension similar to culture-negative controls (2.7% vs 2.6%, adjusted RR, 0.99, CI 0.48 to 2.02) but greater than population controls (adjusted RR, 5.20; 95% CI 2.16 to 12.50). Conclusions CAB is associated with long duration of sick leave and considerable mortality in working-age adults when compared with blood culture-negative controls, and an increased 1-year risk for disability pension when compared with population controls.

Staphylococcus aureus skin and soft tissue infections in primary healthcare in Denmark: a 12-year population-based study

A rise in community-onset Staphylococcus aureus infections has been observed in European countries. To ascertain secular trends of S. aureus infections in primary healthcare in Denmark, we conducted this register-based study in the North Denmark region, during the period 1997–2008. We identified all skin and mucosa specimens obtained by general practitioners and all prescriptions for the preferred oral anti-staphylococcal antibiotic, dicloxacillin. Repeat observations within a 12-month period were excluded prior to the calculation of age and gender standardised incidence rates per 100,000 person-years. We included 108,758 specimens, of which 42,778 (39%) yielded S. aureus. The annual incidence rate of specimens doubled during the study period, reaching 2,399 in 2008. The overall rate of S. aureus isolates increased 2-fold to a stable rate at about 850, but for isolates from children and for impetigo specimens, the increase was steeper, with a peak in 2002. A total of 156,462 dicloxacillin prescriptions had been redeemed and the annual prescription rate increased 2.5-fold, peaking at 3,714 in 2007. In conclusion, the annual rates of specimens, S. aureus infections and dicloxacillin prescriptions more than doubled in primary healthcare during the 12-year study period. A major impetigo epidemic and calls for antibiotic stewardship with increased utilisation of specimens were contributing factors.

Functional status and quality of life after community-acquired bacteraemia: a matched cohort study

Severe bacterial infections may have a prolonged negative effect on subsequent functional status and health-related quality of life. We studied hospitalized patients for changes in functional status and quality of life within 1 year of community-acquired bacteraemia in comparison to blood-culture-negative controls. In a prospectively conducted matched cohort study at Aalborg University Hospital, north Denmark, during 2011-2014, we included 71 medical inpatients with first-time community-acquired bacteraemia. For each bacteraemia patient, we matched one blood-culture-negative inpatient control on age and gender. Functional status and quality of life before and after hospitalization were assessed by Barthel-20 and EuroQol-5D questionnaires. We computed the 3-month and 1-year risk for any deterioration in Barthel-20 score and EuroQol-5D index score, and for a deterioration of ≥10 points in EuroQol-5D visual analogue scale score, and used regression analyses to assess adjusted risk ratios (RR) with 95% CIs. Compared with controls, bacteraemia was associated with an increased 3-month risk for deterioration in functional status as assessed by Barthel-20 score (14% versus 3% with deterioration, adjusted RR 5.1; 95% CI 1.2-22.3). The difference was less after 1 year (11% versus 7% with deterioration, adjusted RR 1.6; 95% CI 0.5-4.5). After 3 months, quality of life had become worse in 37% of bacteraemia patients and 28% of controls by EuroQol-5D index score (adjusted RR 1.3; 95% CI 0.8-2.1), with similar findings after 1 year and by visual analogue scale. In conclusion, community-acquired bacteraemia is associated with increased risk for subsequent deterioration in functional status compared with blood-culture-negative controls, and with a high risk for deterioration in quality of life.

Rare Elizabethkingia anophelis meningitis case in a Danish male

Introduction. Elizabethkingia anophelis is a Gram-negative, aerobic, non-motile rod belonging to the family Flavobacteriaceae. Over the last 5 years, it has emerged as an opportunistic human pathogen involved in neonatal meningitis and sepsis, as well as nosocomial outbreaks. It has been isolated from the midgut of the Anopheles gambiae mosquito, but there is no evidence for a role of the mosquito in human infections, and very little is known regarding the routes of transmission to humans. Recent studies, primarily from South-East Asia, suggest that E. anophelis, and not Elizabethkingia meningoseptica, is the predominant human pathogen of this genus. However, identification to the species level has been difficult due to the limitations of the current MALDI-TOF MS (matrix-associated laser desorption ionization-time of flight MS) systems for correct species identification. Case presentation. Here, we present a rare case of E. anophelis meningitis in a Danish male, who had a travel exposure to Malaysia 7 weeks before hospitalization. A multidrug-resistant Elizabethkingia species was isolated from blood and cerebrospinal fluid, and genomic sequencing was used to characterize the phylogenetic position of the isolate, which was determined as associated with previously described sublineage 11. The patient was successfully treated with intravenous moxifloxacin and rifampicin for 2 weeks with no major sequelae, but we did not find the source of transmission. Conclusion. All clinical microbiologists should be aware of the present limitations of the MALDI-TOF MS systems for correct species identification, and therefore we recommend the use of genome sequencing for the correct identification at the species and sublineage level.

Positive predictive value of ICD-10 diagnosis codes for brain abscess in the Danish National Patient Registry

Purpose To evaluate the positive predictive value (PPV) of ICD-10 diagnosis codes for brain abscess in the Danish National Patient Registry (DNPR). Patients and methods We examined medical records of all patients with a first-time diagnosis code of brain abscess in the DNPR from 2007 to 2016. Patients were categorized with either confirmed or disproved brain abscess using a priori defined criteria. We computed the PPV as the proportion of confirmed diagnoses. Results We identified 709 patients, of whom the medical records could not be retrieved for 15 patients, leaving 694 for further analyses. Of these, 444 had a confirmed brain abscess and 250 had another proven diagnosis, including 47 cases of intracranial empyema. The overall PPV was 64% (95% CI: 60–68) ranging from 24% to 96% among the different codes evaluated. By including only patients with either 1) both a diagnosis and surgical procedure code for brain abscess or 2) patients admitted to hospital with certain primary diagnosis codes (DG060[C,E,F] or DG079B) without newly diagnosed central nervous system (CNS) cancer, spondylodiscitis/intraspinal abscess, or procedure codes for evacuation of intracranial empyema, the PPV increased to 84% (95% CI 80–87) and 89% (395/444) of all confirmed cases were identified. Conclusion The overall PPV of diagnosis codes for brain abscess in the DNPR was moderate. However, by exclusion of newly diagnosed CNS tumors, spondylodiscitis/intraspinal abscess, and intracranial empyemas, the PPV was high and therefore suitable for future registry-based studies of brain abscess.

Return to the workforce following infective endocarditis—A nationwide cohort study

Background The ability to return to work after infective endocarditis (IE) holds important socioeconomic consequences for both patients and society, yet data on this issue are sparse. We examined return to the workforce and associated factors in IE patients of working age. Methods Using Danish nationwide registries, we identified 1,065 patients aged 18–60 years with a first‐time diagnosis of IE (1996–2013) who were part of the workforce prior to admission and alive at discharge. Results One year after discharge, 765 (71.8%) patients had returned to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6 (0.6%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18–40 vs 56–60 years; odds ratio, 2.85; 95% CI, 1.71–4.76) and higher level of education (higher educational level vs basic school; 5.47, 2.05–14.6) and income (highest quartile vs lowest; 3.17, 1.85–5.46) were associated with return to the workforce. Longer length of hospital stay (>90 vs 14–30 days; 0.16, 0.07–0.38); stroke during IE admission (0.38, 0.21–0.71); and a history of chronic kidney disease (0.29, 0.11–0.75), chronic obstructive pulmonary disease (0.31, 0.13–0.71), and malignancy (0.39, 0.22–0.69) were associated with a lower likelihood of returning to the workforce. Conclusions Seven of 10 patients who were part of the workforce prior to IE and alive at discharge were part of the workforce 1 year later. Younger age, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.