Severe infections as risk factors for acute myocardial infarction: a nationwide, Danish cohort study from 1987-2018.

AIMS: Infections have been associated with acute myocardial infarction (AMI), but differences in risk between infection types and age groups are unclear. This study aims to investigate whether infections are associated with subsequent AMI and whether the risk differs across infection sites and age groups. METHODS: Nationwide registers were used to include 702596 adults hospitalized between 1987-2018 with either; pneumonia (n=344319), urinary tract infection (UTI) (n=270101), soft tissue/bone infection (n=66718), central nervous system infection (CNS) (n=17025), or endocarditis (n=4433). Patients were sex- and age-matched with two unexposed controls. Outcome was first-time AMI within ten years. A time-dependent cox proportional hazards model with cut-offs at 30 and 90 days was used for calculating adjusted hazard ratios (HR). RESULTS: Pneumonia, UTI, and soft tissue/bone infection were associated with increased relative rates of AMI compared to matched, unexposed controls. Highest relative rates were found within the first 0-30 days post-exposure; Pneumonia: HR 3.39 (95% CI 3.15-3.65), UTI: HR 2.44 (95% CI 2.21-2.70), Soft tissue/bone infection: HR 1.84 (95% CI 1.45-2.33). Relative rates decreased over time but remained significantly elevated throughout the follow-up period and was increased in all age groups. No association was found for CNS infection and for endocarditis only at 31-90 days, HR 2.28 (95% CI 1.20-4.33). CONCLUSION: Acute infections are associated with increased relative rates of AMI across different infection sites and age groups with higher relative rates found for pneumonia. This indicates that some infections may act as a trigger for AMI with a site and/or pathogen specific risk.

Different infections are associated with an increased risk of acute myocardial infarction for up to ten years after infection but with a particularly high risk within the first 30 days. Exposure to pneumonia, urinary tract infection and soft tissue/bone infection is associated with an increased risk of acute myocardial infarction, particularly within the first 30 days after infection, while exposure to central nervous system infection and endocarditis is not. Pneumonia was associated with a higher risk of myocardial infarction than other infections and the risk was increased in all age groups.

Bacterial aerobic respiration is a major consumer of oxygen in sputum from patients with acute lower respiratory tract infection.

Bacterial aerobic respiration may determine the outcome of antibiotic treatment in experimental settings, but the clinical relevance of bacterial aerobic respiration for the outcome of antibiotic treatment has not been tested. Therefore, we hypothesized that bacterial aerobic respiration is higher in sputum from patients with acute lower respiratory tract infections (aLRTI), than in sputum from patients with chronic LRTI (cLRTI), where the bacteria persist despite antibiotic treatment. The bacterial aerobic respiration was determined according to the dynamics of the oxygen (O2 ) concentration in sputum from aLRTI patients (n = 52). This result was evaluated by comparison to previously published data from patients with cLRTI. O2 consumption resulting in anoxic zones was more frequent in sputum with detected bacterial pathogens. The bacterial aerobic respiration in aLRTI sputum approximated 55% of the total O2 consumption, which was significantly higher than previously published for cLRTI. The bacterial aerobic respiration in sputum was higher in aLRTI patients than previously seen in cLRTI patients, indicating the presence of bacteria with a sensitive physiology in aLRTI. These variations in bacterial physiology between aLRTI patients and cLRTI patients may contribute the huge difference in treatment success between the two patient groups.

The ratio of neutrophil-to-lymphocyte and platelet-to-lymphocyte and association with mortality in community-acquired pneumonia: a derivation-validation cohort study.

RATIONALE: The ratio of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and platelet-to-lymphocyte (PLR) are biomarkers that have shown potential for predicting mortality in several diseases. For patients hospitalized with community-acquired pneumonia (CAP), the prognostic capabilities of these biomarkers are unknown. OBJECTIVE: Investigate whether NLR, MLR or PLR were associated with 90-day mortality in CAP. Further, investigate whether the prediction rule CURB-65 could be improved by adding these biomarkers. METHODS: A derivation-validation study using a Danish multicentre retrospective cohort as the derivation cohort (N = 831) and a European multicentre prospective cohort as the validation cohort (N = 2463). Associations between biomarkers and mortality were assessed using Cox proportional hazard models with adjustments for sex, CURB-65 and comorbidities. A cut-off value for biomarkers was determined using Youden's J Statistics. The performance of CURB-65 with added biomarkers was evaluated using receiver-operating characteristics. RESULTS: In both cohorts increasing NLR and PLR were associated with 90-day mortality. In the derivation cohort, the hazard ratios for NLR and PLR were 1.016 (95% confidence interval (CI) 1.001-1.032, P = 0.038) and 1.001 (95% CI 1.000-1.001, P = 0.035), respectively. Adding these biomarkers to CURB-65 did not improve its performance. CONCLUSIONS: NLR and PLR were associated with 90-day mortality in CAP, but did not improve CURB-65.

Bacterial biofilms predominate in both acute and chronic human lung infections.

BACKGROUND: A basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory-the gold standard of microbiology. OBJECTIVE: To investigate the bacterial architecture in sputum from patients with acute and chronic lung infections. METHODS: Advanced imaging technology was used for quantification and direct comparison of infection types on fresh sputum samples, thereby directly testing the acute versus chronic paradigm. RESULTS: In this study, we compared the bacterial lifestyle (planktonic or biofilm), growth rate and inflammatory response of bacteria in freshly collected sputum (n=43) from patient groups presenting with acute or chronic lung infections. We found that both acute and chronic lung infections are dominated by biofilms (aggregates of bacteria within an extracellular matrix), although planktonic cells were observed in both sample types. Bacteria grew faster in sputum from acute infections, but these fast-growing bacteria were enriched in biofilms similar to the architecture thought to be reserved for chronic infections. Cellular inflammation in the lungs was also similar across patient groups, but systemic inflammatory markers were only elevated in acute infections. CONCLUSIONS: Our findings indicate that the current paradigm of equating planktonic with acute and biofilm with chronic infection needs to be revisited as the difference lies primarily in metabolic rates, not bacterial architecture.

Do-not-resuscitate orders in patients with community-acquired pneumonia: a retrospective study.

BACKGROUND: To investigate the use of do-not-resuscitate (DNR) orders in patients hospitalized with community-acquired pneumonia (CAP) and the association with mortality. METHODS: We assembled a cohort of 1317 adults hospitalized with radiographically confirmed CAP in three Danish hospitals. Patients were grouped into no DNR order, early DNR order (≤48 h after admission), and late DNR order (> 48 h after admission). We tested for associations between a DNR order and mortality using a cox proportional hazard model adjusted for patient and disease related factors. RESULTS: Among 1317 patients 177 (13%) patients received a DNR order: 107 (8%) early and 70 (5%) late, during admission. Patients with a DNR order were older (82 years vs. 70 years, p < 0.001), more frequently nursing home residents (41% vs. 6%, p < 0.001) and had more comorbidities (one or more comorbidities: 73% vs. 59%, p < 0.001). The 30-day mortality was 62% and 4% in patients with and without a DNR order, respectively. DNR orders were associated with increased risk of 30-day mortality after adjustment for age, nursing home residency and comorbidities. The association was modified by the CURB-65 score Hazard ratio (HR) 39.3 (95% CI 13.9-110.6), HR 24.0 (95% CI 11.9-48,3) and HR 9.4 (95% CI: 4.7-18.6) for CURB-65 score 0-1, 2 and 3-5, respectively. CONCLUSION: In this representative Danish cohort, 13% of patients hospitalized with CAP received a DNR order. DNR orders were associated with higher mortality after adjustment for clinical risk factors. Thus, we encourage researcher to take DNR orders into account as potential confounder when reporting CAP associated mortality.

Associations between biomarkers at discharge and co-morbidities and risk of readmission after community-acquired pneumonia: a retrospective cohort study.

To investigate whether hemoglobin, white blood cell count (WBC), urea, sodium, albumin, and C-reactive protein at discharge in patients hospitalized for community-acquired pneumonia (CAP) are associated with 30-day readmission. This study is a retrospective cohort study, which included all adult patients discharged after hospitalization for CAP from three Danish hospitals between January 2011 and July 2012. The outcome was all-cause, unplanned, 30-day readmission. Biomarker concentrations at discharge were transformed into binary variables by using either upper or lower quartiles as cut-off; the upper quartile was used for WBC, urea, and C-reactive protein, and the lower quartile was used for hemoglobin, sodium, and albumin. The study population consisted of 1149 patients. One hundred eighty-four (16.0%) patients were readmitted. Independent risk factors of readmission were WBC ≥ 10.6 cells × 109/L (hazard ratio 1.50; 95% CI, 1.07-2.11) and albumin <32 g/L (hazard ratio 1.78; 95% CI, 1.24-2.54) at discharge and the presence of ≥ 2 co-morbidities (hazard ratio 1.74; 95% CI, 1.15-2.64). When WBC, albumin, and co-morbidities were combined into a risk-stratification tool, there was a step-wise increase in risk of readmission for patients with 1, 2, or 3 risk factors with hazard ratios of 1.76 (95% CI, 1.25-2.49), 2.59 (95% CI, 1.71-3.93), and 6.15 (95% CI 3.33-11.38), respectively. WBC ≥ 10.6 cells × 109/L and albumin < 32 g/L at discharge and the presence of ≥ 2 co-morbidities were independently associated with increased risk of 30-day readmission.

Undiagnosed Diabetes Mellitus in Community-Acquired Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diabetes mellitus is an important risk factor for community-acquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patients with community-acquired pneumonia is largely unknown. We aimed to determine the prevalence of prediabetes, undiagnosed diabetes mellitus, and risk factors associated with undiagnosed diabetes mellitus in a large European community-acquired pneumonia cohort. METHODS: This was a multicenter prospective cohort study of hospitals and private practices in Germany and Austria encompassing 1961 adults with community-acquired pneumonia included in the German Community-Acquired Pneumonia Competence Network (CAPNETZ) study between 2007 and 2014. The prevalence of undiagnosed diabetes mellitus and prediabetes was estimated based on hemoglobin A1c measurements. Logistic regression was used to assess risk factors for undiagnosed diabetes mellitus. RESULTS: Fifteen percent of patients had known diabetes mellitus. Among patients without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes. Male sex (odds ratio [OR], 2.45 [95% confidence interval {CI}, 1.35-4.45]), body mass index ≥25 kg/m2 (OR, 2.64 [95% CI, 1.48-4.72]), and hyperglycemia at admission (6-11 mM: OR, 2.93 [95% CI, 1.54-5.60] and ≥11 mM: OR, 44.76 [95% CI, 17.58-113.98]) were associated with undiagnosed diabetes mellitus. Patients with undiagnosed diabetes mellitus had a higher 180-day mortality rate compared to patients without diabetes mellitus (12.1% vs 3.8%, respectively; P = .001). CONCLUSIONS: Undiagnosed diabetes mellitus was prevalent among community-acquired pneumonia. Male sex, overweight, and hyperglycemia at admission were associated with undiagnosed diabetes mellitus. The long-term mortality among patients with undiagnosed diabetes mellitus was high compared to patients without diabetes mellitus.

The impact of blood glucose on community-acquired pneumonia: a retrospective cohort study.

Hyperglycaemia is common in patients with community-acquired pneumonia (CAP) and is a predictor of severe outcomes. Data are scarce regarding whether this association is affected by diabetes mellitus (DM) and also regarding its importance for severe outcomes in hospital. We determined the impact of blood glucose on severe outcomes of CAP in hospital. We studied 1318 adult CAP patients hospitalised at three Danish hospitals. The association between blood glucose and DM status and severe clinical outcome (admission to an intensive care unit (ICU) and/or in-hospital mortality) was assessed by logistic regression. Models were adjusted for CURB-65 score and comorbidities. 12% of patients had DM. In patients without DM an increase in admission blood glucose was associated with risk for ICU admittance (OR 1.25, 95% CI 1.13-1.39), but not significantly associated with in-hospital mortality (OR 1.10, 95% CI 0.99-1.23). In patients with DM an increase in admission blood glucose was not associated with ICU admittance (OR 1.05, 95% CI 1.00-1.12) or in-hospital mortality (OR 1.05, 95% CI 0.99-1.12). An increase in admission blood glucose (only in patients without DM) was associated with a higher risk for ICU admittance and a trend towards higher in-hospital mortality. DM was not associated with a more severe outcome of CAP.

Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark: a retrospective cohort study.

BACKGROUND: Community-acquired pneumonia (CAP) is a severe infection, with high mortality. Antibiotic strategies for CAP differ across Europe. The objective of the study was to describe the epidemiology of CAP in Denmark and evaluate the prognosis of patients empirically treated with penicillin-G/V monotherapy. METHODS: Retrospective cohort study including hospitalized patients with x-ray confirmed CAP. We calculated the population-based incidence, reviewed types of empiric antibiotics and duration of antibiotic treatment. We evaluated the association between mortality and treatment with empiric penicillin-G/V using logistic regression analysis. RESULTS: We included 1320 patients. The incidence of hospitalized CAP was 3.1/1000 inhabitants. Median age was 71 years (IQR; 58-81) and in-hospital mortality was 8%. Median duration of antibiotic treatment was 10 days (IQR; 8-12). In total 45% were treated with penicillin-G/V as empiric monotherapy and they did not have a higher mortality compared to patients treated with broader-spectrum antibiotics (OR 0.92, CI 95% 0.55-1.53). CONCLUSION: The duration of treatment exceeded recommendations in European guidelines. Empiric monotherapy with penicillin-G/V was commonly used and not associated with increased mortality in patients with mild to moderate pneumonia. Our results are in agreement with current conservative antibiotic strategy as outlined in the Danish guidelines.