IMPORTANCE New-onset atrial fibrillation (AF) is commonly reported in patients with severe infections. However, the absolute risk of thromboembolic events without anticoagulation remains unknown. OBJECTIVE To investigate the thromboembolic risks associated with AF in patients with pneumonia, assess the risk of recurrent AF, and examine the association of initiation of anticoagulation therapy with new-onset AF. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used linked Danish nationwide registries. Participants included patients hospitalized with incident community-acquired pneumonia in Denmark from 1998 to 2018. Statistical analysis was performed from August 15, 2021, to March 12, 2022. EXPOSURES New-onset AF. MAIN OUTCOMES AND MEASURES Thromboembolic events, recurrent AF, and all-cause death. Estimated risks were calculated for thromboembolism without anticoagulation therapy, new hospital or outpatient clinic contact with AF, initiation of anticoagulation therapy, and all-cause death at 1 and 3 years of follow-up. Death was treated as a competing risk, and inverse probability of censoring weights was used to account for patient censoring if they initiated anticoagulation therapy conditioned on AF. RESULTS Among 274196 patients hospitalized for community-acquired pneumonia, 6553 patients (mean age [SD], 79.1 [11.0] years; 3405 women [52.0%]) developed new-onset AF. The 1-year risk of thromboembolism was 0.8% (95% CI, 0.8%-0.8%) in patients without AF vs 2.1% (95% CI, 1.8%2.5%) in patients with new-onset AF without anticoagulation; this risk was 1.4% (95% CI, 1.0%-2.0%) among patients with AF with intermediate stroke risk and 2.8% (95% CI, 23%-34%) in patients with AF with high stroke risk. Three-year risks were 3.5% (95% CI, 2.8%-4.3%) among patients with intermediate stroke risk and 5.3% (95% CI, 4.4%-6.5%) among patients with high stroke risk. Among patients with new-onset AF, 32.9% (95% CI, 31.8%-34.1%) had a new hospital contact with AF, and 14.0% (95% Cl, 13.2%14.9%) initiated anticoagulation therapy during the 3 years after incident AF diagnosis. At 3 years, the all-cause mortality rate was 25.7% (95% CI, 25.6%-25.9%) in patients with pneumonia without AF vs 49.8% (95% CI, 48.6%-51.1%) in patients with new-onset AF. CONCLUSIONS AND RELEVANCE This cohort study found that new-onset AF after community-acquired pneumonia was associated with an increased risk of thromboembolism, which may warrant anticoagulation therapy. Approximately one-third of patients had a new hospital or outpatient clinic contact for AF during the 3-year follow-up, suggesting that AF triggered by acute infections is not a transient, self-terminating condition that reverses with resolution of the infection.

Objectives: To assess the impact of ESBL production on mortality and Length of hospital stay (LOS) of community-onset infections due to Escherichia coli or Klebsiella pneumoniae. Methods: A population-based cohort study including all adult patients hospitalized with a first-time community-onset E. coli or K. pneumoniae bacteraemia or urinary tract infection in the North Denmark Region between 2007 and 2017. For each bacterial agent, we computed 1 year Kaplan-Meier survival curves and cumulative incidence functions of LOS, and by use of Cox proportional hazard regression we computed HRs as estimates of 30 day and 1 year mortality rate ratios (MRRs) and LOS among patients with and without ESBL-producing infections. Results: We included 24 518 cases (among 22350 unique patients), of whom 1018 (4.2%) were infected by an ESBL-producing bacterium. The 30 day cumulative mortality and adjusted MRR (aMRR) in patients with and without ESBL-producing isolates was as follows: E. coli bacteraemia (n =3831), 15.8% versus 14.0%, aMRR =1.01 (95% CI = 0.70-1.45); E. coli urinary tract infection (n =17151), 9.5% versus 8.7%, aMRR =0.97 (95% CI = 0.75-1.26); K. pneumoniae bacteraemia (n = 734), 0% versus 17.2%, aMRR = not applicable; and K. pneumoniae urinary tract infection (n = 2802), 13.8% versus 10.7%, aMRR =1.13 (95% CI = 0.73-1.75). The 1 year aMRR remained roughly unchanged. ESBL-producing E. coli bacteraemia was associated with an increased LOS compared with non-ESBL production. Conclusions: ESBL production was not associated with an increased short- or Long-term mortality in community-onset infections due to E. coli or K. pneumoniae, yet ESBL-producing E. coli bacteraemia was associated with an increased LOS.

Objectives: To investigate and explore temporal changes in risk factors of community-onset extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae bacteraemia in a region with low antibiotic resistance. Methods: Population-based case-control study including 223 cases hospitalized with a first-time community-onset ESBL-producing E. coli and K. pneumoniae bacteraemia, 2214 non-ESBL E. coli and K. pneumoniae bacteraemia controls, and 2228 population controls in the North Denmark Region between 2007 and 2017. We used a conditional logistic regression to compute crude and adjusted (age, gender and co-morbidity) odds ratios (aORs) and 95% CIs of risk factors and compared selected risk factors between 2007-2011 and 2016-2017. Results: Several conventional risk factors of ESBL E. coli or K. pneumoniae were identified compared with the population controls. Compared with the non-ESBL controls, use of fluoroquinolones (aOR 3.56, 95% CI 2.52-5.05), three or more admissions within the recent year (aOR 2.18, 95% CI 1.45-3.28), three or more antibiotic prescriptions within 15-365 days before the admission (aOR 2.18, 95% CI 1.53-3.10), male sex (aOR 2.01, 95% CI 1.50-2.69), admission within 1-91 days (aOR 1.84, 95% CI 1.37-2.48) and antibiotic within 15-91 days (aOR 1.82, 95% CI 1.37-2.42) inferred the highest risk. Assessment of temporal dynamics between 2007-2011 and 2016-2017 revealed a slight reduction in risk factors associated with direct health-care contact (e.g. hospital admission). Conclusions: Recent and frequent hospitalization, and exposure to antibiotics, especially use of fluoroquinolones, appeared to be associated specifically with ESBL production, and focus and interventions should be directed towards these areas. Our results indicated a dissemination of ESBLs into the community. (C) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Background: Data elucidating trends of community-onset extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae infections remain sparse in low prevalence areas. We conducted a population-based study to determine the incidence, temporal trends and co-resistance of community-onset ESBL infections. Methods: We identified all recorded episodes of E. coli and K. pneumoniae bacteraemia and urinary tract infections in adult patients (>15 years) in the North Denmark Region between 2007-2017. Using population-based registries, we obtained information on demographics and place of acquisition, and investigated the standardized incidence rates and temporal trends of community-onset ESBL infections and the associated patterns of co-resistance. Results: A total of 3741 episodes of community-onset ESBL E. coli or K. pneumoniae infections were observed during the study period, with the annual standardized incidence rate increasing from 7.5 to 105 per 100,000 person-years between 2007-2017. The increase was conveyed primarily by a rise in E. coli urinary tract infections shifting from being mainly healthcare-associated to community-acquired. ESBL-producing isolates increased from 0.5 to 4.0% with considerable co-resistance. Conclusion: The proportion of E. coli and K. pneumoniae isolates producing ESBL have increased considerably in the North Denmark Region. The increasing incidence and frequent co-resistance should raise awareness among physicians responsible for empirical antibiotic treatment.

Congenital heart disease (CHD) is associated with risk factors of central nervous system (CNS) infections including infective endocarditis, cardiac shunt physiology, and immune deficiencies. We aimed to investigate the risk of CNS infections in the CHD population compared to the general population. In this cohort study, we used Danish nationwide medical registries to identify individuals diagnosed with CHD at any age, born between 1977 and 2012. For each CHD individual, we matched 10 individuals on sex and birth year from the general population. Subjects were followed until first-time hospital diagnosis of CNS infection, death, emigration, or end of study. We computed cumulative incidences of CNS infections with death as a competing risk, as well as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) adjusted for birth year and sex. We identified 17,550 individuals with CHD (50% male). Among subjects with CHD, the cumulative incidence of CNS infection at age 30 years was 1.0% compared to 0.6% in the general population. The overall HR of CNS infections in CHD subjects relative to the general population was 2.1 (95% CI 1.6–2.7). The HR was 1.9 (95% CI 1.4–2.7) for mild to moderate CHD, 2.1 (95% CI 1.3–3.3) for severe CHD and 3.0 (95% CI 1.1–8.2) for univentricular physiology. The HR for CHD subjects without record of infective endocarditis was 2.0 (95% CI 1.5–2.5). The risk of CNS infections was increased among individuals with CHD compared to the general population, and the risk was not limited to individuals with infective endocarditis.

Abstract Objective To investigate the influence of acetylsalicylic acid (ASA) use on risk and outcome of community-acquired Staphylococcus aureus bacteremia (CA-SAB). Method We used population-based medical databases to identify all patients diagnosed in northern Denmark with first-time CA-SAB and matched population controls from 2000–2011. Categories for ASA users included current users (new or long-term users), former users, and nonusers. The analyses were adjusted for comorbidities, comedication use, and socioeconomic indicators. Results We identified 2638 patients with first-time CA-SAB and 26 379 matched population controls. Compared with nonusers, the adjusted odds ratio (aOR) for CA-SAB was 1.00 (95% confidence interval [CI], 0.88–1.13) for current users, 1.00 (95% CI, 0.86–1.16) for former users, 2.04 (95% CI, 1.42–2.94) for new users, and 0.95 (95% CI, 0.84–1.09) for long-term users. Thirty-day cumulative mortality was 28.0% among current users compared with 21.6% among nonusers, yielding an adjusted hazard rate ratio (aHRR) of 1.02 (95% CI, 0.84–1.25). Compared with nonusers, the aHRR was 1.10 (95% CI, 0.87–1.40) for former users, 0.60 (95% CI, 0.29–1.21) for new users, and 1.06 (95% CI, 0.87–1.31) for long-term users. We observed no difference in the risk or outcome of CA-SAB with increasing ASA dose or by presence of diseases commonly treated with ASA. Conclusions Use of ASA did not seem to influence the risk or outcome of CA-SAB. The apparent increased risk among new users may relate to residual confounding from the circumstances underlying ASA treatment initiation. Our finding of no association remained robust with increasing ASA dose and across multiple patient subsets.

In this review, we discuss Staphylococcus aureus bac-teraemia (SAB), which is a frequent and severe condition associated with high morbidity and mortality. Despite these facts, high-quality data on diagnostic approach, treatment and management of SAB remain scarce. Consequently, evidence-based guidelines concerning antibiotic therapy including the optimal choice of antibiotic drug, route of administration and treatment duration are not available. Thus, controlled clinical trials are urgently needed to increase evidence and to potentially improve the outcome for patients with SAB.

We appreciate Dr Ko and colleagues’ interesting reflections on our findings concerning the influence of statin use on the risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB). Because the aim of our study was to provide epidemiological in vivo data on this association, Ko and colleagues’ review of the literature and considerations on the potential underlying pathophysiologic mechanisms constitute a very valuable supplement to our paper. We agree that the risk of CA-SAB appeared to differ slightly across the different types of statins (simvastatin, atorvastatin, and others). However, because only 9% of current statin users were treated with other statins and because the confidence intervals for the estimates overlapped, these results should be interpreted with caution. As suggested in the letter by Ko et al, we believe that future well-conducted basic and clinical research represents the only way to disentangle the biological mechanisms by which statin treatment may protect against CA-SAB. Statin Use Associated With a Decreased Risk of Community-Acquired Staphylococcus aureus BacteremiaMayo Clinic ProceedingsVol. 93Issue 4PreviewWe read with great interest the recent article by Smit et al1 on statin use associated with a decreased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB), particularly in patients with chronic kidney disease and patients with diabetes. They explained that these results were unlikely due to direct antimicrobial effects of statins on S aureus but more likely due to the pleiotropic effects of statins reducing important isoprenoid intermediates, resulting in decreased bacterial invasion and inducing neutrophil extracellular traps. Full-Text PDF

PurposeData on the systemic dissemination in Staphylococcus aureus bloodstream infection (SAB) remain sparse. We investigated the timing and the sequence of clinical symptoms, diagnostic confirmation, and occurrence of multiple infective foci in relation to three major infective foci.MethodsFrom 2006 to 2011, all adult patients with first-time SAB in Cologne and Freiburg, Germany were followed prospectively. The study was restricted to patients with short-term central venous catheter (CVC)-related SAB, vertebral osteomyelitis (VO), and infective endocarditis (IE). The collection date of the first positive blood culture was used as reference point for determining time to onset of clinical symptoms, microbiological findings, imaging results compatible with focal infection, and occurrence of additional infective foci.ResultsWe included 266 patients with first-time SAB. Among patients with CVC-related SAB, clinical onset, collection of the first positive blood culture, and microbiological confirmation almost coincided. In contrast, among patients with VO or IE, the onset of clinical symptoms most often preceded the collection of the first positive blood culture, and imaging and microbiological confirmation were most frequently obtained subsequent to the SAB diagnosis. CVC-related SAB was infrequently associated with further foci (n=15/15.5%). Conversely, more than one infective focus was observed in 44 (56.4%) patient with VO and 68 (64.8%) patients with IE.ConclusionsThe sequence of clinical symptoms, diagnostic confirmation, and occurrence of multiple infective foci varied considerably with different infective foci in SAB. Based on these results, we propose a pragmatic and evidence-based terminology for the clinical course of SAB and suggest the terms portal of entry, infective focus, multiple infective foci, and dominant infective focus.

Most Staphylococcus aureus isolates can cause invasive disease given the right circumstances, but it is unknown if some isolates are more likely to cause severe infections than others. S. aureus bloodstream isolates from 120 patients with definite infective endocarditis and 121 with S. aureus bacteraemia without infective endocarditis underwent whole-genome sequencing. Genome-wide association analysis was performed using a variety of bioinformatics approaches including SNP analysis, accessory genome analysis and k-mer based analysis. Core and accessory genome analyses found no association with either of the two clinical groups. In this study, the genome sequences of S. aureus bloodstream isolates did not discriminate between bacteraemia and infective endocarditis. Based on our study and the current literature, it is not convincing that a specific S. aureus genotype is clearly associated to infective endocarditis in patients with S. aureus bacteraemia.

Objectives: Female gender has been suggested to be associated with poor outcome in patients with Staphylococcus aureus bacteraemia (SAB), but existing data remain sparse and conflicting. We investigated clinical outcomes in female and male patients with community-acquired (CA-) SAB. Methods: Population-based medical registers were used to conduct a cohort study of all adult patients with CA-SAB in northern Denmark, 2000-2011. Thirty-day mortality after CA-SAB for female and male patients was estimated by the Kaplan-Meier method. Using Cox proportional hazards regression, we computed hazard ratios (HRs) of death according to gender, overall and stratified by age groups, co-morbidity level, and selected major diseases while adjusting for potential confounders. Moreover, we estimated 30-day prevalence proportions for SAB-associated infective endocarditis and osteomyelitis by gender. Results: Among 2638 patients with CA-SAB, 1022 (39%) were female. Thirty-day mortality was 29% (n = 297) in female patients and 22% (n = 355) in male patients, yielding an adjusted HR (aHR) of 1.30 (95% CI, 1.11-1.53). This association appeared robust across age groups, whereas no consistent pattern was observed according to co-morbidity level. Compared with male patients, the prognostic impact of gender was most pronounced among female patients with diabetes (aHR 1.52; 95% CI 1.04-2.21)), and among female patients with cancer (aHR 1.40; 95% CI 1.04-1.90). The 30-day prevalence of infective endocarditis or osteomyelitis did not differ according to gender. Conclusion: Female patients with CA-SAB experienced increased 30-day mortality compared with male patients. Gender should be considered in the triage and risk stratification of CA-SAB patients. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Community-acquired Staphylococcus aureus bacteremia (CA-SAB) is a serious infection with detrimental clinical effects. Chronic diseases constitute some of the most important risk and prognostic factors for CA-SAB. The prevalence of diabetes and chronic heart failure (CHF) is rapidly increasing on a global scale, nevertheless, there are few data available specifically elucidating the influence of these chronic conditions on CA-SAB risk and outcome. Therefore, to extend the current knowledge, we aimed to I) elucidate the impact of different definitions of healthcare-associated (HCA) infection on the prevalence of HCA-SAB, patient characteristics, and mortality, II) to investigate whether diabetes is a risk factor for CA-SAB, III) to ascertain the prognostic influence of diabetes on CA-SAB outcome, and IV) to investigate the influence of CHF on mortality in patients with CA-SAB. The thesis is based on a cross-sectional study, a case-control study, and two cohort studies, all conducted in Northern Denmark, 2000-2011. Utilizing the unique civil registration number assigned to all Danish residents, we linked data from the local departments of clinical microbiology, the Danish Civil Registration System, the Danish National Patient Registry, the LABKA database, and the Aarhus University Prescription Database. In study I, we included 4,385 patients with SAB. The proportion of patients classified as HCA-SAB ranged between 29.8% and 71.7% across five different definitions of HCA infection. Use of different definition of HCA infection also influenced the distribution of patient characteristics, whereas estimates of 30-day mortality remained unchanged (~ 24%). Study II included 2,638 patients with CA-SAB and 26,379 population controls matched by age, gender, and residence. We found diabetes to be strongly associated with an increased risk of CA-SAB (adjusted odds ratio=2.8 (95% CI, 2.5-3.1)). Compared with persons without diabetes, the increased CA-SAB risk was most apparent among patients with type 1 diabetes, patients with a long diabetes history, patients with poor glycemic control, and patients with diabetes complications. In study III, we included 2,638 patients with CA-SAB, of whom 713 (27.0%) had diabetes. After adjustment for potential confounders, the mortality rate ratio for patients with diabetes was 1.01 (95% CI, 0.84-1.20) after 30 days of follow-up. No notable differences in 30-day mortality were observed among patients with and without recent healthcare contacts, and the finding remained robust according to gender, age, comorbidity level, and characteristics of patients with diabetes (e.g. diabetes type and duration of diabetes). In study IV, CHF was associated with a 24% increase in 90-day mortality in patients with CA-SAB. The excess risk of death associated with CHF was most pronounced among patients with concomitant valvular disease and patients using very high doses of loop diuretics, as compared to patient without CHF. In conclusion, we observed considerable variation in the proportion of patients classified as HCA-SAB when different definitions of HCA infection were applied. Diabetes was associated with a substantially increased risk of CA-SAB, whereas CA-SAB outcome was virtually unaffected by diabetes. In contrast, patients with CHF experienced increased 90-day mortality compared with patients without CHF.

BACKGROUND:Patients with diabetes (DM) experience increased risk of Staphylococcus aureus bacteraemia (SAB), but the prognostic impact of diabetes in patients with SAB remain unclear. Therefore, we investigated 30-day all-cause mortality in patients with and without DM.METHODS:Population-based medical databases were used to conduct a cohort study of all adult patients with community-acquired SAB in Northern Denmark, 2000-2011. Using Cox proportional hazards regression, we computed hazard ratios as estimates of 30-day mortality rate ratios (MRRs) among patients with and without DM. We further investigated whether the prognostic impact of DM differed among patients with and without recent preadmission healthcare contacts (within 30 days of the current hospitalization) and by age, sex, marital status, level of comorbidity, and DM-related characteristics (e.g., duration of DM and presence of DM complications).RESULTS:Among 2638 SAB patients, 713 (27.0%) had DM. Thirty-day cumulative mortality was 25.8% in patients with DM and 24.3% in patients without DM, for an adjusted MRR (aMRR) of 1.01 (95% confidence interval (CI), 0.84-1.20). In analyses with and without recent healthcare contacts, the corresponding aMRRs were 0.84 (95% CI, 0.62-1.14) and 1.13 (95% CI, 0.91-1.41), respectively. Compared to patients without DM, the aMRR was 0.94 (95% CI, 0.74-1.20) for male patients with DM and 1.13 (95% CI, 0.87-1.47) for female patients with DM. The prognostic influence of DM on mortality did not differ notably with age, level of comorbidity, or characteristics of patients with DM.CONCLUSION:Patients with DM and community-acquired SAB did not experience higher 30-day mortality than patients without DM.

OBJECTIVE:Patients with diabetes may experience higher risk of Staphylococcus aureus bacteremia (SAB) than patients without diabetes due to decreased immunity or coexisting morbidities. We investigated the risk of community-acquired (CA) SAB in persons with and without diabetes.DESIGN:Using population-based medical databases, we conducted a case-control study of all adults with first-time CA-SAB and matched population controls in Northern Denmark, 2000-2011.METHODS:Based on conditional logistic regression, we computed odds ratios (ORs) of CA-SAB according to diabetes. We further assessed whether the risk of CA-SAB differed according to various diabetes-related characteristics (e.g. duration of diabetes, glycemic control, and presence of diabetes complications).RESULTS:We identified 2638 patients with incident CA-SAB, of whom 713 (27.0%) had diabetes, and 26,379 matched population controls (2495 or 9.5% with diabetes). Individuals with diabetes had a substantially increased risk of CA-SAB compared with population controls (adjusted OR = 2.8 (95% confidence interval (CI): 2.5-3.1)). Duration of diabetes of ≥10 years and poor glycemic control conferred higher risk estimates, with an adjusted OR = 2.3 (95% CI: 1.9-2.7) for diabetes with Hba1c < 7% (< 53 mmol/mol) and an adjusted OR = 5.7 (95% CI: 4.2-7.7) for diabetes with Hba1c ≥9% (≥75 mmol/mol). The risk of CA-SAB was particularly high in patient with diabetes complications: adjusted OR = 5.5 (95% CI: 4.2-7.2) with presence of microvascular complications and OR = 7.0 (95% CI: 5.4-9.0) with combined macro- and microvascular complications.CONCLUSIONS:Diabetes is associated with a substantially increased risk of CA-SAB, particularly in patients with diabetes of long duration, poor glycemic control, and diabetes complications.

An abstract is not available for this content so a preview has been provided. As you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Patients with chronic heart failure (CHF) may experience higher mortality of Staphylococcus aureus bacteremia (SAB) than patients without CHF due to insufficient cardiovascular responses during systemic infection. We investigated 90-day mortality in SAB patients with and without CHF.

We investigated whether different definitions of healthcare-associated infection influenced the prevalence, characteristics, and mortality of patients with Staphylococcus aureus bacteremia. With different definitions, the proportion of patients classified as having healthcare-associated S. aureus bacteremia varied substantially and the distribution of patient characteristics was influenced, whereas 30-day mortality remained robust.

The incidence of candidaemia is increasing on a global scale. Secondary intraocular involvement is a rare but serious complication, which can cause considerable visual damage. Hence, current national and international guidelines recommend ophthalmological examination of all patients with verified candidaemia in order to ensure adequate therapy and reduce the risk of visual impairment. We present a case illustrating that initial symptoms and findings of ocular candidiasis may often be subtle which emphasizes the importance of consistent adherence to these guidelines.